This is an application for a Mentored, Patient-Oriented Research Career Development Award (K23) entitled, "Effects of Vascular Disease in Mild Cognitive Impairment." The aim of this study is to examine the effects of vascular factors in Mild Cognitive Impairment (MCI). Although MCI is associated with an increased risk of dementia, MCI is a heterogeneous condition with multiple etiologies, presentations, and outcomes. Vascular disease may be an under-recognized determinant of MCI and may account for some of the heterogeneity among individuals with MCI. Vascular risk factors and related white matter hyperintensities (WMH) confer an increased risk of MCI, and the term 'vascular MCI' has been proposed to refer to patients with cognitive impairment of presumed vascular origin. However, few studies have investigated the role of vascular disease in MCI and the cognitive profiles and long-term outcomes of vascular-related MCI remain unknown. The proposed study was designed to investigate longitudinal relationships between midlife vascular risk, later-life WMH, and cognition among individuals with MCI. Primary aims are: 1) to determine the extent to which midlife vascular risk predicts later-life WMH, and 2) to determine the extent to which WMH predict cognitive declines over 2 years among individuals with MCI. Participants will include 120 individuals from the Framingham Heart Study (FHS), a population based study of risk factors for heart disease, stroke, and dementia. The FHS has been in existence since 1948 and provides a well-characterized population in which to examine the role of vascular factors in MCI. Vascular causes of cognitive impairment likely are more preventable and treatable than are other causes of cognitive impairment in aging, and an improved understanding of the role of vascular disease in MCI may inform interventions to reduce age-related cognitive impairment and dementia. The candidate, Patricia Boyle, Ph.D., completed a NIA-sponsored Postdoctoral Individual National Research Service Award and is an Assistant Professor in the Department of Neurology at the Boston University School of Medicine. The integrated research and training program described in this application extends her prior work and involves new training in: 1) the neurobiology of aging, 2) vascular and genetic risk assessment, and 3) quantitative neuroimaging techniques. Training will involve intensive instruction with mentors, didactic coursework and seminars, and collaborations with senior FHS investigators. The knowledge and skills gained via the proposed multidisciplinary training will facilitate Dr. Boyle's rapid development into an independent investigator in patient-oriented, aging research. Findings from the proposed study will provide the foundation for a program of research investigating the predictors of age-related cognitive decline and will be used as pilot data in future grant applications to be submitted prior to the completion of this award.